Boushel 2012 Am J Physiol Regul Integr Comp Physiol

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Boushel RC, Fuentes T, Hellsten Y, Saltin B (2012) Opposing effects of nitric oxide and prostaglandin inhibition on muscle mitochondrial VO2 during exercise . Am J Physiol Regul Integr Comp Physiol 303:94-100.

» PMID: 22552792 Open Access

Boushel RC, Fuentes T, Hellsten Y, Saltin B (2012) Am J Physiol Regul Integr Comp Physiol

Abstract: Nitric oxide (NO) and prostaglandins (PG) together play a role in regulation blood flow during exercise. NO also regulates mitochondrial oxygen consumption through competitive binding to cytochrome c oxidase. Indomethacin both uncouples and inhibits the electron transport chain in a concentration-dependent manner, and thus inhibition of NO and PG may regulate both muscle oxygen delivery and utilization. The purpose of this study was to examine the independent and combined effects of NO and PG blockade (L-NMMA and indomethacin respectively) on mitochondrial respiration in human muscle following knee extension (KE) exercise. Mitochondrial respiration was measured ex-vivo by high-resolution respirometry in saponin-permeabilized fibers following 6 min KE in control (CON, n=8), arterial infusion of LNMMA (n=4) and Indo (n=4) followed by combined inhibition of NO and PG (L-NMMA + Indo, n=8). ADP-stimulated State 3 respiration with substrates for Complex I (glutamate, malate) was reduced 50% by Indo. State 3 O(2) flux with Complex I and II substrates was reduced less with both Indo (20%) and L-NMMA + Indo (15%) compared to CON. The results indicate that indomethacin reduces State 3 mitochondrial respiration primarily at Complex I of the respiratory chain while blockade of NO by addition of L-NMMA counteracts the inhibition of Indo. This metabolic effect in concert with a reduction of blood flow likely accounts for in-vivo changes in muscle O2 consumption during combined blockade of NO and PG.

Keywords: Muscle oxygen delivery and utilization, NO and PG blockade

O2k-Network Lab: SE Stockholm Boushel RC, CA Vancouver Boushel RC

Labels: MiParea: Respiration, Pharmacology;toxicology 

Stress:Oxidative stress;RONS  Organism: Human  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 

Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, NS  HRR: Oxygraph-2k